The objective of this research is to develop efficient and rapid procedures for synthesizing polynucleotides possessing any desired sequence of nucleotides. Attention will be given to syntheses conducted on insoluble polymer supports since the support technique offers the best prospect for substantially reducing the labor involved in preparing predesignated polynucleotides. In addition to studying new methods for forming phosphodiester and phosphotriester links, we shall investigate the synthesis of phosphoramidate analogs of oligonucleotides and the feasibility of using these analogs as templates for enzymatic synthesis. The goal is the development of a new approach to polynucleotide synthesis that involves the chemical synthesis on polymer supports of oligonucleotides, the linking together of these oligonucleotides chemically by means of phosphoramidate bonds, and utilization of the polynucleotide analogs thus prepared as templates for enzymatic synthesis of complementary polynucleotides possessing natural phosphodiester internucleotide links exclusively. The synthetic polynucleotides and the phosphoramidate polynucleotide analogs with prescribed base sequences should prove to be valuable tools for the study of genetic processes occurring in living cells and in investigations aimed at controlling diseases that have been associated with nucleic acids. Bibliographic references: "Synthesis of Phosphoramidate Diester Nucleotides via the Phosphite-Azide Coupling Method," R.L. Letsinger and G.A. Heavner, Tetrahedron Letters, 147 (1975); "Use of the Azido Group in the Synthesis of 5'-Terminal Aminodeoxythymidine Oligonucleotides," W.S. Mungall, G.L. Greene, G.A. Heavner, and R.L. Letsinger, J. Org. Chem., 40, 1659 (1975).